Dataset Information

Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial.

ABSTRACT:

Background

Matrix-associated autologous chondrocyte implantation (ACI) is a well-established treatment for cartilage defects. High-level evidence at midterm follow-up is limited, especially for ACI using spheroids (spherical aggregates of ex vivo expanded human autologous chondrocytes and self-synthesized extracellular matrix).

Purpose

To assess the safety and efficacy of 3-dimensional matrix-associated ACI using spheroids to treat medium to large cartilage defects on different locations in the knee joint (patella, trochlea, and femoral condyle) at 5-year follow-up.

Study design

Cohort study; Level of evidence, 2.

Methods

A total of 75 patients aged 18 to 50 years with medium to large (4-10 cm²), isolated, single cartilage defects, International Cartilage Repair Society grade 3 or 4, were randomized on a single-blind basis to treatment with ACI at 1 of 3 dose levels: 3 to 7, 10 to 30, or 40 to 70 spheroids/cm² of defect size. Outcomes were assessed via changes from baseline Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee score, and modified Lysholm assessments at 1- and 5-year follow-up. Structural repair was evaluated using MOCART (magnetic resonance observation of cartilage repair tissue) score. Treatment-related adverse events were assessed up to 5 years for all patients. The overall KOOS at 12 months was assessed for superiority versus baseline in a 1-sample, 2-sided t test.

Results

A total of 73 patients were treated: 24 in the low-dose group, 25 in the medium-dose group, and 24 in the high-dose group. The overall KOOS improved from 57.0 ± 15.2 at baseline to 73.4 ± 17.3 at 1-year follow-up (P < .0001) and 76.9 ± 19.3 at 5-year follow-up (P < .0001), independent of the applied dose. The different defect locations (patella, trochlea, and weightbearing part of the femoral condyles; P = .2216) and defect sizes (P = .8706) showed comparable clinical improvement. No differences between the various doses were observed. The overall treatment failure rate until 5 years was 4%. Most treatment-related adverse events occurred within the first 12 months after implantation, with the most frequent adverse reactions being joint effusion (n = 71), arthralgia (n = 14), and joint swelling (n = 9).

Conclusion

ACI using spheroids was safe and effective for defect sizes up to 10 cm² and showed maintenance of efficacy up to 5 years for all 3 doses that were investigated.

Registration

NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).

SUBMITTER: Hoburg A

PROVIDER: S-EPMC8777354 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAutologous chondrocyte implantation (ACI) is an established method for treating cartilage defects in the knee of adult patients. However, less is known about its effectiveness in adolescents.HypothesisThird-generation matrix-associated ACI (MACI) using spheroids (co.don chondrosphere/Spherox) is an effective and safe treatment for articular cartilage defects in adolescents aged 15 to 17 years, with outcomes comparable with those for young adults aged 18 to 34 years.Study designCohort study; Level of evidence, 3.MethodsA total of 71 patients (29 adolescents, 42 young adults) who had undergone ACI using spheroids were evaluated retrospectively in this multicenter study. For adolescents, the mean defect size was 4.6 ± 2.4 cm2, and the follow-up range was 3.5 to 8.0 years (mean, 63.3 months). For young adults, the mean defect size was 4.7 ± 1.2 cm2, and the follow-up range was 3.8 to 4.3 years (mean, 48.4 months). At the follow-up assessment, outcomes were assessed by using validated questionnaires (Knee injury and Osteoarthritis Outcome Score [KOOS], International Knee Documentation Committee [IKDC] subjective knee evaluation form and current health assessment form, and modified Lysholm score), the magnetic resonance observation of cartilage repair tissue (MOCART) score, and if relevant, time to treatment failure. Safety was assessed by the treatment failure rate.ResultsNo significant difference between the 2 study groups was found for KOOS, IKDC, or MOCART scores, with all patients achieving high functional values. A significant difference was found in the modified Lysholm score, favoring the young adult group over the adolescent group (22.3 ± 1.9 vs 21.0 ± 2.4, respectively; P = .0123). There were no differences between the rates of treatment failure, with 3% in the adolescent group and 5% in the young adult group.ConclusionThird-generation MACI using spheroids is a safe and effective treatment for large cartilage defects of the knee in adolescents at midterm follow-up. Outcomes are comparable with those for young adults after ACI.

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